Ovotesticular Difference of Sex Development: Genetic Background, Histological Features, and Clinical Management.

BACKGROUND: Ovotesticular disorder/difference of sex development (DSD) refers to the co-presence of testicular and ovarian tissue in one individual. Childhood management is challenging as there are many uncertainties regarding etiology, gonadal function, and gender outcome. SUMMARY: Ovotesticular DSD should mainly be considered in 46,XX children with atypical genitalia and normal adrenal steroid profiles. Various underlying genetic mechanisms have been described. Histological assessment of ovotestes requires expert revision and has many pitfalls. Neonatal sex assignment is essential, but as gender outcome is unpredictable, this should be regarded as provisional until a stable gender identity has developed. Therefore, it is crucial not to perform any irreversible medical or surgical procedure in affected individuals until adolescents can give their full informed consent. Gonadal function mostly allows for spontaneous pubertal development; however, fertility is compromised, especially in boys. Specific long-term outcome data for ovotesticular DSD are lacking but can be extrapolated from studies in other DSD populations. KEY MESSAGES: Management of ovotesticular DSD has changed in recent years, prioritizing the child's future right for autonomy and self-determination. The benefits and pitfalls of this new approach have not been documented yet and require intensive monitoring on an international scale.

True hermaphroditism with dysgerminoma: A case report.

INTRODUCTION: True hermaphroditism is a rare and usually sporadic disorder. It is defined by the presence of both ovarian and testicular tissues together as ovotestis. PATIENT CONCERNS: In this study, we reported a rare true hermaphroditism case with dysgerminoma. A 49-year-old woman developed masses in both inguinal regions for 30 years. Recently 3 months, the patient found that the size of mass in her left inguinal region was significantly increased. DIAGNOSIS: After surgical resection, the results of immunohistochemical examination in left mass revealed a dysgerminoma with positive expression of placental alkaline phosphatase and octamer-binding transcription factor 3/4, and right mass was a cryptorchidism. Chromosomal analysis revealed the karyotype 46, XY. Combined immunohistochemical and karyotype analysis, a diagnosis of true hermaphroditism with dysgerminoma was made. INTERVENTIONS: Radiotherapy combined with chemotherapy after tumor resection was used to improve her prognosis. Hormone replacement therapy with conjugated estrogen and medroxyprogesterone acetate were used to maintain her female characteristics. OUTCOMES: The patient underwent hormonal replacement and has been well for 6 months. CONCLUSION: The positive expression of placental alkaline phosphatase and octamer-binding transcription factor 3/4 could be 2 diagnosis markers of dysgerminoma. Surgery combined with radiotherapy and chemotherapy could improve the prognosis of dysgerminoma. Moreover, hormone replacement therapy with conjugated estrogen and medroxyprogesterone acetate was very helpful to maintain the female characteristic of patients with true hermaphroditism.

Successful second delivery outcome using refrozen thawed testicular sperm from an infertile male true hermaphrodite with a 46, XX/46, XY karyotype: case report.

We report a successful second delivery of a healthy infant fathered using refrozen thawed testicular sperm from an infertile male chimera. We also examined sex chromosome distribution of the seminiferous tubule. Intracytoplasmic sperm injection (ICSI) was performed using the remaining refrozen testicular sperm, which had been stored during the first treatment. Biopsied testicular cells were examined by fluorescence in situ hybridization (FISH) and the peripheral lymphocyte karyotype was tested using a G-band. Following ICSI, a second pregnancy was established, and a healthy girl was successfully delivered at 40 gestational weeks without complications. Although the husband's lymphocyte chromosomal analysis revealed a 46, XX [28]/46, XY [2] karyotype, the seminiferous tubule cells on histological examination by FISH were chimeric sex chromosome type XX [18]/XY [82]. In conclusion, this is a very rare case report of a successful subsequent delivery of a healthy infant (46, XX) from an infertile true hermaphrodite (46, XX/46, XY) using refrozen thawed testicular sperm. The seminiferous tubule cells' karyotype ratio differed from that of the lymphocytes.

Regional variations in the management of testicular or ovotesticular disorders of sex development.

Disorders of sex development arise in parts of the world with different socio-economic and cultural characteristics. We wished to determine the regional variations in the management of these conditions. A questionnaire was e-mailed to the 650 members of the European Society for Paediatric Endocrinology (ESPE), an international society with a mainly European membership but which also includes professionals from other continents. Results were subjected to statistical analysis. A total of 62 answers were received, a satisfactory rate given that not all members are involved in this issue. Results show statistically significant regional differences for available diagnostic resources, age of the patient at gender assignment, parameters considered important for gender assignment, and timing of discussion of various issues with parents and patient. The regional variations exist not only between different continents, as already demonstrated by others, but also between Northern, Latin and Eastern European countries. This suggests that 'one-fits-all' guidelines for management are not appropriate.

A 3-year-old boy with ovotestes: gender reassignment and surgical management.

OBJECTIVE: We report a male patient with ovotesticular disorder of sex development (OTDSD), resulting from structurally abnormal Y chromosome. CASE REPORT: A 3-year-old boy was admitted to the Surgical Pediatric Department for masculinizing reconstruction. He had a clitorophallus, bifid scrotum, perineal hypospadias and bilateral impalpable gonads. Pelvic ultrasound and laparoscopy showed a uterus and two gonads with primary ovarian follicles. Chromosome analysis detected a mos 47,XX,mar/46,XX karyotype. Complex genetic evaluation revealed that the marker was Yp isochromosome. Surgical care included a feminizing genitoplasty and separation of the gonads with total excision of testicular tissue. CONCLUSIONS: The presented case emphasizes the importance of a systematic approach to the investigation and management of the patients with ovotesticular DSD. It also raises the important issue about gender reassignment in intersex individuals in mid-childhood.

Long-term outcome of ovotesticular disorder of sex development: a single center experience.

OBJECTIVES: To describe the clinical features of children with ovotesticular disorder of sex development (DSD) and to review cases of ovotesticular DSD in Japan. METHODS: Medical records of eight children diagnosed with ovotesticular DSD at our institute during the past 17 years were retrospectively evaluated. A review of 165 reported cases of ovotesticular DSD from Japanese institutions was carried out. RESULTS: Mean follow up was 8.2 years for six children, with two children lost to follow up. Mean age at first presentation was 2.4 months. All children were Japanese. The most common initial manifestation was ambiguous genitalia. The female:male ratio as the sex of rearing was 1:1. Gender reassignment, from male to female, was carried out in one child at 4-months-old. Genital surgery was always carried out in early childhood as per family desire. Appropriate gonadal tissue was preserved except for one child. No gonadal tumors were detected during follow up. Spontaneous pubertal development occurred in one boy. In reviewing Japanese data, the frequency of testes was higher than in other ethnicities and this was related to the higher incidence of 46,XY. CONCLUSIONS: According to our experience, most families in Japan desire early genital surgery in the case of ovotesticular DSD. Chromosomal and gonadal distributions in patients with ovotesticular DSD differ between Japanese and other ethnic groups. Treatment for these patients needs to be provided after considering the cultural and social backgrounds of DSD in Japan.

46,XX/SRY-negative true hermaphrodite.

OBJECTIVE: To describe genetic evaluation and response to surgery and letrozole therapy of a 46,XX/SRY-negative true hermaphrodite. DESIGN: Case report. SETTING: University Medical Center. PATIENT(S): Nineteen-year-old male with penile hypospadias, micropenis, and crytorchidism at the time of birth. INTERVENTION(S): Unilateral gonadectomy, and contralateral conservative gonadal surgery, followed by therapy with letrozole. MAIN OUTCOME MEASURE(S): Histopathologic, genetic and hormonal studies. RESULT(S): Genetic analysis showed that the subject was 46,XX/SRY-negative. Gonadectomy of the left gonad was performed at 16 years. The gonad resected was an ovotestes. The patient's estradiol was high (492±25 pmol/L), whereas the testosterone was low (4.2±0.5 nmol/L). Nineteen months later, conservative gonadal surgery of the contralateral gonad was performed to resect ovarian tissue, and treatment with letrozole was started. During letrozole treatment, testosterone was significantly increased (8±0.7 nmol/L), but estradiol was not changed (323±118 pmol/L). After letrozole withdrawal, testosterone did not decreased significantly (6.9±0.4 nmol/L), estradiol showed an oscillating pattern and a gonadal ultrasound showed an ovoid structure, which appeared to correspond to a follicle. At that time, estradiol was elevated (393 pmol/L). CONCLUSION(S): We present the case of a 46,XX/SRY-negative phenotypic male with bilateral ovotestes. Conservative gonadal surgery should be performed only when all ovarian tissue can be resected. Our results suggest that letrozole is not an adequate treatment for 46,XX true hermaphrodite males with ovotestes.

Seminoma in a male phenotype 46XX true hermaphrodite.

Although true hermaphrodite is uncommon, it has been reported in more than 400 individuals. Tumours arising in the gonads of true hermaphrodite is a very rare finding and only very few cases have been reported in the literature. We report a case of a 35-year-old phenotype man with bilateral undescended testis with lump hypogastrium. On examination, he had an ovotestis on one side and pure seminoma arising in testis on the other side. The seminoma arising in the left undescended testis was successfully treated by excision and combination chemotherapy. Cytogenetic studies revealed that 46XX karyotype with primer specific for the sex-determining region of the Y chromosome was negative. The karyotypic abnormality noticed in the patient is also reviewed in the article.

True hermaphroditism: clinical profile and management of six patients from North India.

True hermaphroditism (TH) is an uncommon cause of genital ambiguity. This is a retrospective compilation of six cases of true hermaphroditism seen at our institute over the last one and a half decades. Clinical presentation was wide-ranging, with age at presentation varying from 2 months to 41 years and symptoms ranging from ambiguous genitalia to a lower abdominal mass. All patients had perineoscrotal hypospadias with varying degrees of labioscrotal fusion. Clinically, gonads were not palpable in four cases and internally an ovotestis was observed in half of them. Karyotyping was 46, XX in all except one. The majority of the patients were reared as males. True hermaphroditism (TH) forms an important differential in the diagnostic algorithm of ambiguous genitalia especially if gonads are not palpable and congenital adrenal hyperplasia has been ruled out.